The Extracellular Signal-regulated Kinase Pathway Regulates the Phosphorylation of 4E-BP1 at Multiple Sites

Abstract

The phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), a potent stimulator of Erk, leads to the phosphorylation of 4E-BP1 and its dissociation from eIF4E. In contrast to agonists such as insulin, this occurs independently of PKB activation. In this report, we investigate the mechanism by which TPA regulates 4E-BP1 phosphorylation. and its release from eIF4E. In this case, the phosphorylation of these sites was also blocked by inhibitors of MEK or by rapamycin. In conclusion, the Erk pathway, via mecha…